Neutrophil extracelluar traps in COVID-19
Neutrophil extracelluar traps in COVID-19
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DOI：
10.1172/jci.insight.138999
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发表时间：
2020-06-04
期刊：
影响因子：
8
通讯作者：
Knight, Jason S.
中科院分区：
文献类型：
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作者：
Zuo, Yu;Yalavarthi, Srilakshmi;Knight, Jason S.
在2019冠状病毒病（COVID-19）的严重病例中，病毒性肺炎会发展为呼吸衰竭。中性粒细胞胞外陷阱（NETs）是由嗜中性粒细胞释放的染色质、杀微生物蛋白和氧化酶组成的胞外网，以遏制感染。然而，如果没有适当的调节，NET有可能传播炎症和微血管血栓形成-包括急性呼吸窘迫综合征患者的肺部。我们现在报告说，COVID-19患者的血清中游离DNA、髓过氧化物酶-DNA（MPO-DNA）和瓜氨酸化组蛋白H3（Cit-H3）水平升高;后两种是NET的特异性标志物。强调了这些发现的潜在临床意义，游离DNA与急性期反应物（包括C-反应蛋白、D-二聚体和乳酸脱氢酶）以及中性粒细胞绝对计数密切相关。MPO-DNA与游离DNA和中性粒细胞绝对计数相关，而Cit-H3与血小板水平相关。重要的是，接受机械通气的住院患者的游离DNA和MPO-DNA均高于呼吸室内空气的住院患者。最后，来自COVID-19患者的血清在体外触发了对照中性粒细胞的NET释放。未来的研究应该调查纵向队列中循环NET的预测能力，并确定NET在多大程度上可能成为严重COVID-19的新治疗靶点。
In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have the potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. We now report that sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3); the latter 2 are specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute-phase reactants, including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.